Abstract
In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.
Highlights
Plague is a zoonotic infectious disease caused by the Gramnegative bacterium Yersinia pestis
We examined liver, spleen, lung, kidney, heart and lymph node tissues from Chinese-origin rhesus macaques immunized with SV1, SV2, and EV76 that were subcutaneously infected with virulent Y. pestis 141
Tissue injury after infection with Y. pestis After challenging with virulent Y. pestis 141, the lungs, livers, kidneys, lymph nodes, spleens, and hearts of the animals immunized with SV1, SV2, and EV76, and the control animals immunized with adjuvant were collected, fixed in 10% neutral buffered formalin, and prepared for hematoxylin and eosin (HE) staining
Summary
Plague is a zoonotic infectious disease caused by the Gramnegative bacterium Yersinia pestis. Plague is an awful infectious disease that afflicts human populations, leading to millions of deaths. Most human plague cases clinically present as one of three primary forms—bubonic, septicemic and pneumonic. Bubonic plague is the most common form of the disease, which occurs when Y. pestis is inoculated into the skin. Primary bubonic or septicemic plague is usually caused by fleabite among rodent reservoir hosts and most human cases are usually transmitted from an infected rodent via the bite of an infected flea, whereas pneumonic plague usually spread by respiratory droplets. Patients with primary bubonic plague can develop secondary septic or pneumonic infection, which can be spread from personto-person via respiratory droplets generated from sneezing and coughing [3]
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